RT Journal Article
T1 Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study.
A1 Charbit-Henrion, Fabienne
A1 Parlato, Marianna
A1 Hanein, Sylvain
A1 Duclaux-Loras, Remi
A1 Nowak, Jan
A1 Begue, Bernadette
A1 Rakotobe, Sabine
A1 Bruneau, Julie
A1 Fourrage, Cecile
A1 Alibeu, Olivier
A1 Rieux-Laucat, Frederic
A1 Levy, Eva
A1 Stolzenberg, Marie-Claude
A1 Mazerolles, Fabienne
A1 Latour, Sylvain
A1 Lenoir, Christelle
A1 Fischer, Alain
A1 Picard, Capucine
A1 Aloi, Marina
A1 Dias, Jorge Amil
A1 Hariz, Mongi Ben
A1 Bourrier, Anne
A1 Breuer, Christian
A1 Breton, Anne
A1 Bronsky, Jiri
A1 Buderus, Stephan
A1 Cananzi, Mara
A1 Coopman, Stephanie
A1 Cremilleux, Clara
A1 Dabadie, Alain
A1 Dumant-Forest, Clementine
A1 Gurkan, Odul Egritas
A1 Fabre, Alexandre
A1 Fischer, Aude
A1 Diaz, Marta German
A1 Gonzalez-Lama, Yago
A1 Goulet, Olivier
A1 Guariso, Graziella
A1 Gurcan, Neslihan
A1 Homan, Matjaz
A1 Hugot, Jean-Pierre
A1 Jeziorski, Eric
A1 Karanika, Evi
A1 Lachaux, Alain
A1 Lewindon, Peter
A1 Lima, Rosa
A1 Magro, Fernando
A1 Major, Janos
A1 Malamut, Georgia
A1 Mas, Emmanuel
A1 Mattyus, Istvan
A1 Mearin, Luisa M
A1 Melek, Jan
A1 Navas-Lopez, Victor Manuel
A1 Paerregaard, Anders
A1 Pelatan, Cecile
A1 Pigneur, Bénédicte
A1 Pais, Isabel Pinto
A1 Rebeuh, Julie
A1 Romano, Claudio
A1 Siala, Nadia
A1 Strisciuglio, Caterina
A1 Tempia-Caliera, Michela
A1 Tounian, Patrick
A1 Turner, Dan
A1 Urbonas, Vaidotas
A1 Willot, Stephanie
A1 Ruemmele, Frank M
A1 Cerf-Bensussan, Nadine
K1 Genetics and molecular epidemiology
K1 TNGS
K1 VEO-IBD
K1 Monogenic disorders
K1 Paediatrics
AB An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases [VEO-IBD]. The present study aimed at defining how next-generation sequencing [NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment. A total of 207 children were recruited in 45 paediatric centres through an international collaborative network [ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD [n = 185] or an anamnesis suggestive of a monogenic disorder [n = 22]. Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing [WES] of parents-child trios. Genetic findings were validated clinically and/or functionally. Molecular diagnosis was achieved in 66/207 children [32%]: 61% with small bowel inflammation, 39% with colitis and perianal lesions, and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations, and identified large exonic copy number variations previously missed by WES. Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD.
PB Oxford Univesity Press
YR 2018
FD 2018-05-18
LK http://hdl.handle.net/10668/12496
UL http://hdl.handle.net/10668/12496
LA en
NO Charbit-Henrion F, Parlato M, Hanein S, Duclaux-Loras R, Nowak J, Begue B, et al. Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study. J Crohns Colitis. 2018 Aug 29;12(9):1104-1112
NO This work was supported by ERC-2013-AdG-339407-IMMUNOBIOTA, Investissement d’Avenir ANR-10-IAHU-01, Fondation des Maladies Rares, and Association François Aupetit. FC-H was supported by a fellowship from INSERM. JN received a fellowship from the Polish National Science Centre [2015/16/T/NZ5/00168].
DS RISalud
RD Apr 7, 2025